Interdisciplinary Nanoscience Center, Aarhus University DK-8000 Aarhus, Denmark;
Centre for Cellular Signal Patterns (CellPAT), Aarhus University, Aarhus DK-8000, Denmark.
Proc Natl Acad Sci U S A. 2021 Dec 14;118(50). doi: 10.1073/pnas.2112942118.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created an urgent need for new technologies to treat COVID-19. Here we report a 2'-fluoro protected RNA aptamer that binds with high affinity to the receptor binding domain (RBD) of SARS-CoV-2 spike protein, thereby preventing its interaction with the host receptor ACE2. A trimerized version of the RNA aptamer matching the three RBDs in each spike complex enhances binding affinity down to the low picomolar range. Binding mode and specificity for the aptamer-spike interaction is supported by biolayer interferometry, single-molecule fluorescence microscopy, and flow-induced dispersion analysis in vitro. Cell culture experiments using virus-like particles and live SARS-CoV-2 show that the aptamer and, to a larger extent, the trimeric aptamer can efficiently block viral infection at low concentration. Finally, the aptamer maintains its high binding affinity to spike from other circulating SARS-CoV-2 strains, suggesting that it could find widespread use for the detection and treatment of SARS-CoV-2 and emerging variants.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）大流行迫切需要新技术来治疗 COVID-19。在这里，我们报告了一种 2'-氟保护的 RNA 适体，它与 SARS-CoV-2 刺突蛋白的受体结合域（RBD）具有高亲和力，从而阻止其与宿主受体 ACE2 的相互作用。与每个刺突复合物中的三个 RBD 匹配的三聚体 RNA 适体增强了结合亲和力，降至低皮摩尔范围。适体-刺突相互作用的结合模式和特异性得到了生物层干涉测量、单分子荧光显微镜和体外流动诱导分散分析的支持。使用病毒样颗粒和活 SARS-CoV-2 的细胞培养实验表明，适体，在更大程度上，三聚体适体可以在低浓度下有效阻止病毒感染。最后，该适体对来自其他循环 SARS-CoV-2 株的刺突保持高结合亲和力，表明它可能被广泛用于 SARS-CoV-2 和新兴变体的检测和治疗。
